Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Collaboration Solves Structure of Herpes Virus Protein, Provides New Drug Directions

27.07.2010
The mechanism by which a herpes virus invades cells has remained a mystery to scientists, but now research from Tufts University and the University of Pennsylvania reveals the unusual structure of a key member of the protein complex that allows a herpes virus to invade cells.

The new map details an essential piece of the herpes virus “cell-entry machinery,” providing scientists with a new target for antiviral drugs.

The research was published online in the journal Nature Structural & Molecular Biology.

Researchers at Tufts and Penn used X-ray crystallography along with cell microscopy techniques to study the structure and function of the cell-entry protein fusion events carried out by HSV-2. The research has resulted in a map of an important protein complex required to trigger herpes virus infection, setting the stage for new therapeutics that may prevent the virus's access to cells.

Most viruses need cell-entry proteins called fusogens in order to invade cells. Scientists have known that the herpes virus fusogen does not act alone, requiring a complex of two other viral cell-entry proteins. In this study, researchers determined the structure of this key protein complex and realized it did not resemble the structure of other known fusogens.

“This unexpected result leads us to believe that this protein complex is not a fusogen itself but that it regulates the fusogen,” said senior author Ekaterina Heldwein, assistant professor of molecular and microbiology at Tufts University School of Medicine. “We also found that certain antibodies interfere with the ability of this protein complex to bind to the fusogen, evidence that antiviral drugs that target this interaction could prevent viral infection.”

“We hope that determining the structure of this essential piece of the herpes virus cell-entry machinery will help us answer some of the many questions about how herpes virus initiates infection,” said first author Tirumala K. Chowdary, a postdoctoral associate at Tufts. “Knowing the structures of cell-entry proteins will help us find the best strategy for interfering with this pervasive family of viruses.”

There is no cure for herpes viruses. Upon infection, the viruses remain in the body for life and can stay inactive for long periods of time. When active, however, different herpes viruses can cause cold sores, blindness, encephalitis or cancers. More than half of Americans are infected with herpes simplex virus type 1, HSV-1, by the time they reach their 20s. About one in six Americans is infected with herpes simplex virus type 2, HSV-2, which is the virus responsible for genital herpes. Complications of HSV-2, a sexually-transmitted disease, include recurrent painful genital sores, psychological distress and, if transmitted from mother to child, potentially fatal infections in newborns.

Herpes viruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpes viruses inexplicably require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but, unlike other members of its class, it does not function alone.

“We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2,” said Roselyn J. Eisenberg, professor of microbiology at the University of Pennsylvania School of Veterinary Medicine. “gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen.”

“We propose that gH-gL activates gB for fusion, possibly through direct binding,” said Gary Cohen, professor of microbiology at the University of Pennsylvania School of Dental Medicine. “Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.”

The study was conducted by Heldwein and Chowdary of Tufts School of Medicine; Cohen, Tina Cairns and Doina Atanasiu of the Department of Microbiology at Penn Dental Medicine; and Eisenberg at Penn Vet.

Research was funded by the National Institutes of Health, the National Institute of Allergy and Infectious Diseases and the Pew Scholar Program in Biomedical Sciences.

Jordan Reese | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Life Sciences:

nachricht A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Quantum bugs, meet your new swatter

20.08.2018 | Information Technology

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>